Feedback control of organ size precision is mediated by BMP2-regulated apoptosis in the Drosophila eye.

Biological processes are intrinsically noisy, and yet, the result of development-like the species-specific size and shape of organs-is usually remarkably precise. This precision suggests the existence of mechanisms of feedback control that ensure that deviations from a target size are minimized. Still, we have very limited understanding of how these mechanisms operate. Here, we investigate the problem of organ size precision using the Drosophila eye. The size of the adult eye depends on the rates at which eye progenitor cells grow and differentiate. We first find that the progenitor net growth rate results from the balance between their proliferation and apoptosis, with this latter contributing to determining both final eye size and its variability. In turn, apoptosis of progenitor cells is hampered by Dpp, a BMP2/4 signaling molecule transiently produced by early differentiating retinal cells. Our genetic and computational experiments show how the status of retinal differentiation is communicated to progenitors through the differentiation-dependent production of Dpp, which, by adjusting the rate of apoptosis, exerts a feedback control over the net growth of progenitors to reduce final eye size variability.

Increase in Postoperative Body Mass Index in Patients After Total Knee Arthroplasty.

Objectives The aim of this is to investigate the changes in body mass index (BMI) following knee arthroplasty and to evaluate their impact on patient-reported outcomes and functional evaluations. Methods This observational study included 90 patients who underwent total knee arthroplasty (TKA) and were followed up for a median period of 2.6 years. BMI measurements were recorded before and after surgery, and patient-reported outcomes and functional evaluations were assessed using standardized scales and tests. Results Following TKA, BMI increased statistically significantly (Wilcoxon signed-rank test, p < 0.000). In addition, half of the patients experienced an increase in BMI, with 32% moving up in their BMI category. However, there were no clinically significant differences in patient-reported outcomes or functional evaluations between the group that gained BMI and the group that maintained or lost BMI. Conclusion This study reveals that patients tend to have increased BMI following TKA. However, these BMI changes do not significantly impact patient-reported outcomes or functional evaluations. It underscores the importance of patient education regarding healthy lifestyle habits, including diet and physical activity, to address postoperative weight gain effectively.

Similar Patient Satisfaction and Quality of Life Improvement Achieved with TKA and THA According to the Goodman Scale: A Comparative Study.

Background: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are effective treatments for severe knee and hip osteoarthritis. Historically, TKA has been associated with lower satisfaction than THA, but recent advances in knee surgery have led to lower dissatisfaction rates. This study aimed to compare the satisfaction and self-reported improvement in the quality of life of two cohorts of patients who underwent TKA and THA, respectively. Methods: This observational study compared two previously published cohorts of patients who underwent THA and TKA in a single university center. The Goodman scale was used to assess satisfaction and self-perception of improved quality of life after TKA and THA at a minimum one-year follow-up. Propensity score matching was used to balance age, gender, and follow-up between groups. Significance was set at 0.05. Results: The study included a total of 105 THAs and 131 TKAs. Both groups had high levels of satisfaction with pain relief, ability to do house/yard work, and overall satisfaction, with above 90% satisfaction rates. Regarding improvement in quality of life, both groups had 86% of patients reporting improvement as "much better." After propensity score matching, no significant difference was found between THA and TKA for any of the comparisons made using the Goodman scale. Conclusions: The study showed that both TKA and THA resulted in high levels of satisfaction and improvement in quality of life. There was no significant difference in satisfaction rates between TKA and THA, contrary to the historical trend of lower satisfaction rates for TKA.

Anterior knee pain and sit-up tests predicts patients' satisfaction and improvement in quality of life after anterior stabilized total knee replacement without patellar resurfacing.

PURPOSE: The purpose of this study was to assess patient satisfaction and identify risk factors for dissatisfaction after anterior stabilised conventional total knee arthroplasty (TKA) without patellar resurfacing, using the Goodman score. METHODS: We conducted a cross-sectional study using data from our institutional database from 1 January 2018 to 1 March 2021. Patients who underwent TKA with the Vanguard® Cruciate Retaining Anterior Stabilized Knee System (Zimmer Biomet, Warsaw, Indiana, USA) without patellar replacement were included. Patients with other bearing surfaces (posterior stabilised or medial congruent) or diagnosed with infection or instability were excluded. Patients' reported outcomes, body mass index (BMI), passive range of motion, the timed up-and-go test, sit-up test, and algometry were assessed. Patients were also asked if they had anterior knee pain. Satisfaction was assessed using the Goodman scale, and logistic multivariate regression was used to identify variables associated with dissatisfaction and perceived improvement in quality of life. RESULTS: A total of 131 TKA patients were included in the study. The median satisfaction score was 100 (interquartile range [IQR], 87.5 to 100), with the 75-point threshold at the 90th percentile according to Section A of Goodman. Section B of Goodman showed that 113 TKA patients (86.26%) reported "great improvement" or "more than I ever dreamed." Multivariate logistic regression revealed that anterior knee pain (OR 5.16, 95% CI 1.24 to 21.39), the sit-up test (OR 0.63, 95% CI 0.49 to 0.81), and BMI (OR 0.84, 95% CI 0.70 to 0.99) were significantly associated with patient dissatisfaction and a worse perceived improvement in quality of life. The receiver operating characteristics curve for the models had areas under the curve of 0.83 (95% CI 0.69 to 0.97) and 0.82 (95% CI 0.70 to 0.94), respectively. CONCLUSION: Anterior stabilised TKA without patellar resurfacing can achieve 90% satisfaction and 86% improvement in quality of life. To improve these results, it is essential to prevent and treat anterior knee pain and enhance quadriceps strength. LEVEL OF EVIDENCE: Level III (retrospective cohort study).

Quantitative Relationships Between Growth, Differentiation, and Shape That Control Drosophila Eye Development and Its Variation.

The size of organs is critical for their function and often a defining trait of a species. Still, how organs reach a species-specific size or how this size varies during evolution are problems not yet solved. Here, we have investigated the conditions that ensure growth termination, variation of final size and the stability of the process for developmental systems that grow and differentiate simultaneously. Specifically, we present a theoretical model for the development of the Drosophila eye, a system where a wave of differentiation sweeps across a growing primordium. This model, which describes the system in a simplified form, predicts universal relationships linking final eye size and developmental time to a single parameter which integrates genetically-controlled variables, the rates of cell proliferation and differentiation, with geometrical factors. We find that the predictions of the theoretical model show good agreement with previously published experimental results. We also develop a new computational model that recapitulates the process more realistically and find concordance between this model and theory as well, but only when the primordium is circular. However, when the primordium is elliptical both models show discrepancies. We explain this difference by the mechanical interactions between cells, an aspect that is not included in the theoretical model. Globally, our work defines the quantitative relationships between rates of growth and differentiation and organ primordium size that ensure growth termination (and, thereby, specify final eye size) and determine the duration of the process; identifies geometrical dependencies of both size and developmental time; and uncovers potential instabilities of the system which might constraint developmental strategies to evolve eyes of different size.

Anticipating Environmental Burdens in Research and Innovation Projects. Application to the Case of Active and Healthy Ageing.

In this paper; for research and innovation projects without environmental goals; a procedure is proposed to operationalize the anticipation and reflexivity of environmental concerns in the initial phases. By using the expert knowledge of specialists; we have first conducted a study to identify the general environmental topics relevant in any kind of research and innovation project not addressing the environment. In a second phase; a strategy is proposed to rank order the topics in terms of environmental relevance by means of the Analytic Hierarchy Process. To illustrate it; the case of Information and Communication Technologies for Active and Healthy Ageing is used because of its increasing importance; and because normal environmental targets are not considered. Results show that; in this case; the most relevant topic to be considered is the primary energy consumption by sources; followed by hazardous solid waste and consumption of non-renewable and scarce materials. According to the experts; these should be the main issues to be considered regarding the environmental sustainability of the outputs of such research and innovation projects. In conclusion; this paper contributes to a better understanding of how to promote a wider integration of environmental sustainability in research and innovation when environmental goals are not initially included.

Dynamic Hh signalling can generate temporal information during tissue patterning.

The differentiation of tissues and organs requires that cells exchange information in space and time. Spatial information is often conveyed by morphogens: molecules that disperse across receiving cells to generate signalling gradients. Cells translate such concentration gradients into space-dependent patterns of gene expression and cellular behaviour. But could morphogen gradients also convey developmental time? Here, by investigating the developmental role of Hh on a component of the Drosophila visual system, the ocellar retina, we have discovered that ocellar cells use the non-linear gradient of Hh as a temporal cue, collectively performing the biological equivalent of a mathematical logarithmic transformation. In this way, a morphogen diffusing from a non-moving source is decoded as a wave of differentiating photoreceptors that travels at constant speed throughout the retinal epithelium.

Impact of a Mass Gathering Alcohol Sobering Facility on Emergency Resources.

OBJECTIVE: Alcohol consumption has been implicated as an important factor driving the demand for medical care at mass gatherings. Patients exhibiting signs of possible alcohol intoxication are frequently diverted from traditional medical support facilities located within mass gathering events due to their disruptive behavior or need for prolonged observation. This conventional strategy can place additional stress on Emergency Medical Services (EMS) and Emergency Department (ED) resources. The purpose of this study was to determine if incorporation of an on-site alcohol sobering facility to supplement existing on-site medical support resources was associated with changes in EMS and ED resource utilization during an annual mass gathering. METHODS: This retrospective observational study of a large, annual mass gathering included prospectively collected data from before and after the deployment of an on-site alcohol sobering facility. One year of EMS data along with 2 years of ED data from the pre-deployment time period were compared to 3 years of post-deployment data. The primary outcomes for this study were the number of EMS transports and ED visits. RESULTS: Average single day event attendance was 176,116 during the 2012-13 time period before the ACS was deployed and 183,544 in the 3 years following. The odds of an EMS transport from the event to the ED decreased in the post-deployment period, OR 0.37 (95% CI = 0.16-0.86; p = 0.01). ED volume increased by 7.23% (p = 0.56) and ED LOS increased by 1.29% (p = 0.97) in the post-deployment period. CONCLUSION: This study reports on a unique strategy to improve resource utilization at large mass gatherings and the impact of this strategy on EMS and ED resource utilization. It appears that the addition of an on-site alcohol sobering facility to existing medical support services was associated with a significant decrease in EMS transports but no change in ED resource utilization. Further work is needed to determine if these findings can be reproduced at other mass gatherings.

Polycomb protein RING1A limits hematopoietic differentiation in myelodysplastic syndromes.

Genetic lesions affecting epigenetic regulators are frequent in myelodysplastic syndromes (MDS). Polycomb proteins are key epigenetic regulators of differentiation and stemness that act as two multimeric complexes termed polycomb repressive complexes 1 and 2, PRC1 and PRC2, respectively. While components and regulators of PRC2 such as ASXL1 and EZH2 are frequently mutated in MDS and AML, little is known about the role of PRC1. To analyze the role of PRC1, we have taken a functional approach testing PRC1 components in loss- and gain-of-function experiments that we found overexpressed in advanced MDS patients or dynamically expressed during normal hematopoiesis. This approach allowed us to identify the enzymatically active component RING1A as the key PRC1 component in hematopoietic stem cells and MDS. Specifically, we found that RING1A is expressed in CD34+ bone marrow progenitor cells and further overexpressed in high-risk MDS patients. Knockdown of RING1A in an MDS-derived AML cell line facilitated spontaneous and retinoic acid-induced differentiation. Similarly, inactivation of RING1A in primary CD34+ cells augmented erythroid differentiation. Treatment with a small compound RING1 inhibitor reduced the colony forming capacity of CD34+ cells from MDS patients and healthy controls. In MDS patients higher RING1A expression associated with an increased number of dysplastic lineages and blasts. Our data suggests that RING1A is deregulated in MDS and plays a role in the erythroid development defect.

¿Se ha sobrevalorado la razón normalizada internacional (INR)? / Has the international normalized ratio (INR) been overestimated?

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